龙胆泻肝汤对胆囊胆固醇结石小鼠胆固醇代谢的影响  

Effects of Longdan Xiegan Decoction on cholesterol metabolism in gallbladder cholesterol stone mice

作　　者：闵莉[1,2] 章小燕 王素英 梁文娜 沈建英[1,2] 王荷颖 MIN Li;ZHANG Xiaoyan;WANG Suying;LIANG Wenna;SHEN Jianying;WANG Heying(College of Traditional Chinese Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;Key Laboratory of Traditional Chinese Medicine Syndrome Research in Fujian Provincial Universities,Fuzhou 350122,China)

机构地区：[1]福建中医药大学中医学院,福州350122 [2]中医证研究福建省高校重点实验室,福州350122

出　　处：《中华中医药杂志》2024年第7期3410-3415,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81603541);福建省自然科学基金面上项目(No.2021J01928,No.2017J01543)。

摘　　要：目的:通过小鼠胆固醇代谢中密切相关基因尼曼-匹克C1样蛋白(NPC1L1)、腺苷三磷酸结合盒转运蛋白(ABC)G5、ABCG8的表达变化,探讨龙胆泻肝汤对胆囊胆固醇结石(CS)小鼠胆固醇代谢的影响。方法:将32只雄性C57BL/6J小鼠随机分为空白组12只,造模组20只,采用胆固醇致石饲料诱导法塑造CS小鼠模型,8周后,两组各随机取4只小鼠取材查看胆囊结石情况。造模成功后,造模组随机分为模型组(8只)和龙胆泻肝汤组(8只),龙胆泻肝汤组予龙胆泻肝汤13.8g·kg^(-1)·d^(-1)灌胃,空白组和模型组给予等量0.9%氯化钠溶液灌胃,干预4周。HE染色观察各组小鼠肝脏与小肠的组织形态;ELISA检测血清胆固醇(TC)与甘油三酯(TG)、胆汁TC与胆汁酸(TBA)含量;q-PCR及Western Blot分别检测小鼠肝脏和小肠组织中NPC1L1、ABCG5/ABCG8 mRNA与蛋白表达水平。结果:与空白组比较,模型组小鼠血清TC、TG和胆汁TC、TBA均显著升高(P<0.01,P<0.05);模型组小肠NPC1L1mRNA与蛋白表达显著上调(P<0.01),ABCG5/G8mRNA与蛋白表达显著下调(P<0.01);肝组织中NPC1L1mRNA与蛋白表达均显著下调(P<0.01),而ABCG5/G8mRNA与蛋白表达均显著上调(P<0.01)。与模型组比较,龙胆泻肝汤组小鼠肝和小肠组织病理形态均明显改善;龙胆泻肝汤组血清中TC、TG和胆汁中TC、TBA显著降低(P<0.01,P<0.05);龙胆泻肝汤组小肠NPC1L1mRNA和蛋白表达显著下调(P<0.01,P<0.05),小肠ABCG5/G8mRNA和蛋白表达均显著上调(P<0.01,P<0.05);肝NPC1L1 mRNA和蛋白表达显著上调(P<0.01),肝ABCG5/G8mRNA和蛋白表达显著下调(P<0.05,P<0.01)。结论:龙胆泻肝汤能够改善CS模型小鼠胆固醇代谢异常,肠、肝组织NPC1L1、ABCG5/G8表达异常引起胆固醇过饱和可能是CS湿热蕴结的分子生物学基础之一。Objective:The effect of Longdan Xiegan Decoction on cholesterol metabolism in cholesterol stone(CS)mice was investigated through the expression changes of closely related genes NPCIL1,ABCG5 and ABCG8.Methods:A total of 32 male C57BL/6J mice were randomly divided into a blank group(n=12)and a model group(n=20).CS mouse models were established using lithogenic feed induction method.After 8 weeks,4 mice from each group were randomly selected to observe the condition of gallbladder stones.After successful modeling,the modeling group was randomly divided into model group(8 mice)and Longdan Xiegan Decoction group(8 mice).The Longdan Xiegan Decoction group was orally administered with Longdan Xiegan Decoction 13.8 g·kg^(-1)d^(-1),while the blank group and model group were orally administered with equal amounts of physiological saline for 4 weeks of intervention.Tissue morphology of the liver and small intestine of each group of mice were observed by using hematoxylin eosin staining.ELISA was used to detect serum cholesterol(TC)and triglycerides(TG),as well as bile TC and bile acid(TBA)levels.The mRNA and protein expression levels of NPCIL1 and ABCG5/ABCG8 were detected by q-PCR and Western Blot in mouse liver and small intestine tissues,respectively.Results:Compared with the blank group,the serum TC,TG,and bile TC,TBA of the model group mice increased significantly(P<0.01,P<0.05),the mRNA and protein expression of NPCIL1 in the small intestine of the model group were significantly upregulated(P<0.01),while the mRNA and protein expression of ABCG5/G8 were significantly downregulated(P<0.01),the mRNA and protein expression of NPCIL1 in liver tissue were significantly downregulated(P<0.01),while the mRNA and protein expression of ABCG5/G8 were significantly upregulated(P<0.01).Compared with the model group,the pathological morphology of the liver and small intestine tissues in the Longdan Xiegan Decoction group was significantly improved,the serum TC,TG,and bile TC,TBA in the Longdan Xiegan Decoction group were significan

关 键 词：胆囊 胆固醇结石 尼曼-匹克C1样蛋白1 腺苷三磷酸结合盒转运蛋白G5/G8 龙胆泻肝汤 胆固醇代谢 机制 

分 类 号：R285.5[医药卫生—中药学]